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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
2,2',2''-nitrilotriethanol
EC Number:
203-049-8
EC Name:
2,2',2''-nitrilotriethanol
Cas Number:
102-71-6
Molecular formula:
C6H15NO3
IUPAC Name:
2,2',2''-nitrilotriethanol
Test material form:
liquid: viscous
Specific details on test material used for the study:
- Name of test material (as cited in study report): triethanolamine
- Analytical purity: 88.5%
- Impurities (identity and concentrations): MEA<0.12; DEA 6.0; TEA-1EO 5.3

Test animals

Species:
rat
Strain:
other: Cox CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
- 20 male and 20 female per group
- Diet: ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: standard chow
Duration of treatment / exposure:
91 days
Frequency of treatment:
continuously
Doses / concentrationsopen allclose all
Dose / conc.:
250 other: mg/kg bw
Dose / conc.:
500 other: mg/kg bw
Dose / conc.:
1 000 other: mg/kg bw
No. of animals per sex per dose:
20
Control animals:
yes, concurrent no treatment
Details on study design:
Post-exposure period: no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
FOOD EFFICIENCY: Yes
HAEMATOLOGY: Yes
Sacrifice and pathology:
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
One male from the mid-dose group and one female from the low-dose group displayed symptoms of inner ear infection.
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
The only adverse significant differences noted were in body weight gain in the female rats of the mid-dose group.
Please see the Table 1. in Section "Any other information on results incl. tables"
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Please see the Table 2. in Section "Any other information on results incl. tables"
Food efficiency:
effects observed, non-treatment-related
Description (incidence and severity):
The only adverse significant differences noted were in feed efficiency in the female rats of the mid-dose group.
Please see the Table 3. in Section "Any other information on results incl. tables"
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
The only abnormality observed was a slightly elevated WBC in one animal. This change was not considered significant. All other values are within normal limits and there were no significant differences between treatment groups.
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Please see the Table 4. and 5. in Section "Any other information on results incl. tables"
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Tissue alterations observed were mild and were not considered significant. No lesions were found which followed a pattern of agent-induced toxicity.
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 other: mg/kg bw
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no significant effects at highest dose tested

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

Additiononal information: One rat escaped from its cage during the third week of the test and had to be eliminated because of contamination.

Table 1. Bodyweight gain

 

males

females

Control

341±30

157±23

250 mg/kg

339±35

170±13

500 mg/kg

331±28

151±15

1000 mg/kg

329±32

161±22

 

Table 2. Feed consumption

 

males

females

Control

2143±155

1542±105

250 mg/kg

2073±165

1592±108

500 mg/kg

2076±282

5166±115

1000 mg/kg

2091±155

1604±123

 

Table 3. Feed efficiency

 

males

females

Control

15.95±0.98

10.18±1.1

250 mg/kg

16.35±0.97

10.72±0.67

500 mg/kg

15.56±0.84

8.62±2.7

1000 mg/kg

15.75±0.99

9.99±0.88

   

Table 4. Organ to bodyweight ratio (LIVER)

 

males

females

Control

38.2±3.3

42.1±12.2

250 mg/kg

41.6±3.7

39.9±3.3

500 mg/kg

45.9±6.9

44.6±1.0

1000 mg/kg

49.6±2.9

45.3±2.9

 

Table 5. Organ to bodyweight ratio (KIDNEY)

 

males

females

Control

7.6±0.6

8.1±0.3

250 mg/kg

9.3±1.3

10.2±1.4

500 mg/kg

9.2±0.7

11.1±0.7

1000 mg/kg

10.4±1.4

10.3±1.4

Applicant's summary and conclusion